<div class="csl-bib-body">
<div class="csl-entry">Honeder, S., Bradić, I., Küntzel, K. B., Schittmayer-Schantl, M., Kratky, D., & Birner-Grünberger, R. (2023, September 27). <i>Competitive activity-based proteomic profiling reveals tissue-specific off-targets of lipase inhibitors</i> [Poster Presentation]. APMRS 2023, Innsbruck, Austria. http://hdl.handle.net/20.500.12708/189178</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/189178
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dc.description.abstract
Activity-based proteomic profiling (ABPP) enables the functional study of enzymes by employing small molecule probes that bind covalently to the active site of an enzyme. Activity-based probes can pene-trate cells and tissues and thereby allow enzymes to be targeted/labeled in their native state. Probes can be designed to target individual enzymes or whole enzyme groups, which makes ABPP a versatile protein profiling technique. In competitive ABPP, these small molecule probes compete with endoge-nous substrates for the enzyme's active site by displacing the substrate and blocking the active site terminally by covalently binding to it.
Lipid hydrolases are essential enzymes that play a pivotal role in maintaining healthy cellular function by breaking down complex lipids into simpler components, and their dysregulation can contribute to a range of diseases, including obesity, cardiovascular disorders, and metabolic syndromes. Lipase inhib-itors serve as valuable tools for unraveling the intricate roles of lipases in diverse diseases, enabling researchers to manipulate lipid metabolism and study the downstream effects on cellular pathways and physiological processes. The application of lipase inhibitors in studies could present difficulties due to the possible engagement of various off-target effects on different enzymes, potentially leading to am-biguous outcomes and a lack of specificity toward a particular enzyme.
We therefore set out to employ competitive ABPP to identify novel lipase inhibitor off-targets by combin-ing the use of a small molecule probe targeting serine hydrolases together with treatment of inhibitors against the lipolytic enzymes Adipose Triglyceride Lipase (ATGL), Hormone Sensitive Lipase (ATGL), Monoacylglycerol Lipase (MGL) or Lysosomal Acid Lipase (LAL) in murine primary hepatocytes as well as in bone marrow-derived macrophages (BMDM). With this method, we identify several known as well as some unknown off-targets for MGL inhibitor JZL-184 and LAL inhibitors Lalistat-1 and Lalistat-2. We further observe differences in the lipase activity profiles between hepatocytes and BMDM.
In conclusion, our comprehensive approach utilizing competitive ABPP uncovers tissue-specific off-tar-gets of prominent lipase inhibitors, shedding light on their potential implications for cellular function and underscoring the significance of considering tissue variability when studying lipase inhibition effects.
en
dc.description.sponsorship
FWF Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
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dc.language.iso
en
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dc.subject
activity-based proteomics
en
dc.subject
tissue specific
en
dc.subject
lipase inhibitors
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dc.title
Competitive activity-based proteomic profiling reveals tissue-specific off-targets of lipase inhibitors
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dc.title.alternative
Competitive activity-based proteomic profiling reveals tissue-specific off-targets of widely used lipase inhibitors
en
dc.type
Presentation
en
dc.type
Vortrag
de
dc.contributor.affiliation
Medical University of Graz, Austria
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dc.contributor.affiliation
Medical University of Graz, Austria
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dc.contributor.affiliation
Medical University of Graz, Austria
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dc.contributor.affiliation
Medical University of Graz, Austria
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dc.relation.grantno
F 7309-B21
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dc.type.category
Poster Presentation
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tuw.project.title
Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten
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tuw.researchTopic.id
M6
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tuw.researchTopic.name
Biological and Bioactive Materials
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tuw.researchTopic.value
100
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tuw.linking
https://biocrates.com/event/apmrs-2023/
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tuw.publication.orgunit
E164-01-3 - Forschungsgruppe Bioanalytik
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tuw.author.orcid
0000-0002-7201-6293
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tuw.author.orcid
0000-0003-4732-8831
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tuw.author.orcid
0000-0003-3249-655X
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tuw.author.orcid
0000-0003-1357-7573
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tuw.author.orcid
0000-0003-3950-0312
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tuw.event.name
APMRS 2023
en
tuw.event.startdate
27-09-2023
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tuw.event.enddate
29-09-2023
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tuw.event.online
On Site
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tuw.event.type
Event for scientific audience
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tuw.event.place
Innsbruck
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tuw.event.country
AT
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tuw.event.presenter
Honeder, Sophie
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tuw.event.track
Single Track
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wb.sciencebranch
Chemie
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wb.sciencebranch
Biologie
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wb.sciencebranch
Anatomie, Pathologie, Physiologie
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wb.sciencebranch.oefos
1040
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wb.sciencebranch.oefos
1060
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wb.sciencebranch.oefos
3011
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wb.sciencebranch.value
40
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wb.sciencebranch.value
30
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wb.sciencebranch.value
30
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item.openairetype
conference poster not in proceedings
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item.fulltext
no Fulltext
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item.grantfulltext
restricted
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item.languageiso639-1
en
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item.openairecristype
http://purl.org/coar/resource_type/c_18co
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item.cerifentitytype
Publications
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crisitem.project.funder
FWF - Österr. Wissenschaftsfonds
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crisitem.project.grantno
F 7309-B21
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crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
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crisitem.author.dept
Medical University of Graz
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crisitem.author.dept
Medical University of Graz
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crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
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crisitem.author.dept
Medical University of Graz
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crisitem.author.dept
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
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crisitem.author.orcid
0000-0003-4732-8831
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crisitem.author.orcid
0000-0003-3249-655X
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crisitem.author.orcid
0000-0003-1357-7573
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crisitem.author.orcid
0000-0003-3950-0312
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crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
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crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
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crisitem.author.parentorg
E164 - Institut für Chemische Technologien und Analytik
